Protein 4.1, also known as Beatty's Protein, is a protein associated with the cytoskeleton that in humans is encoded by the EPB41gene. Protein 4.1 is a major structural element of the erythrocytemembrane skeleton. It plays a key role in regulating membrane physical properties of mechanical stability and deformability by stabilizing spectrin-actin interaction. Protein 4.1 (80 kD) interacts with spectrin and short actin filaments to form the erythrocyte membrane skeleton. Mutations of spectrin and protein 4.1 are associated with elliptocytosis or spherocytosis and anemia of varying severity.
A schematic diagram representing the relationships between cytoskeletal molecules as relevant to hereditary elliptocytosis.
Elliptocytosis is a hematologic disorder characterized by elliptically shaped erythrocytes and a variable degree of hemolytic anemia. Inherited as an autosomal dominant, elliptocytosis results from mutation in any one of several genes encoding proteins of the red cell membrane skeleton. The form discussed here is the one found in the 1950s to be linked to Rh blood group and more recently shown to be caused by a defect in protein 4.1. 'Rh-unlinked' forms of elliptocytosis are caused by mutation in the alpha-spectrin gene (MIM 182860), the beta-spectrin gene (MIM 182870), or the band 3 gene (MIM 109270) [supplied by OMIM].
^Mattagajasingh SN, Huang SC, Hartenstein JS, Benz EJ (September 2000). "Characterization of the interaction between protein 4.1R and ZO-2. A possible link between the tight junction and the actin cytoskeleton". J. Biol. Chem. 275 (39): 30573–85. doi:10.1074/jbc.M004578200. PMID10874042.
Conboy JG, Chan JY, Chasis JA, Kan YW, Mohandas N (1991). "Tissue- and development-specific alternative RNA splicing regulates expression of multiple isoforms of erythroid membrane protein 4.1". J. Biol. Chem. 266 (13): 8273–80. PMID2022644.
Horne WC, Prinz WC, Tang EK (1990). "Identification of two cAMP-dependent phosphorylation sites on erythrocyte protein 4.1". Biochim. Biophys. Acta. 1055 (1): 87–92. doi:10.1016/0167-4889(90)90095-U. PMID2171679.
Schischmanoff PO, Winardi R, Discher DE, Parra MK, Bicknese SE, Witkowska HE, Conboy JG, Mohandas N (1995). "Defining of the minimal domain of protein 4.1 involved in spectrin-actin binding". J. Biol. Chem. 270 (36): 21243–50. doi:10.1074/jbc.270.36.21243. PMID7673158.